I propose to target liposomes containing iron oxide particles (magnetosomes) and a drug to defined areas in rat by the use of an external magnetic field. The encapsulation of iron oxide particles in liposomes (magnetosomes) in high yield is made possible by a new technique developed in this laboratory (Szoka and Papahadjopoulos, Proc. Nat. Acad. Sci. USA, 75, 4194-4198 (1978). Furthermore, magnetosomes can be prepared in defined size ranges by extrusion through polycarbonate membranes, an important parameter for in vivo drug delivery. The magnetosomes will be examined in an in vitro analog of the circulatory system to determine the effects of the intensity of the magnetic field and flow rate through the system on the localization of magnetosomes. The location of the magnetosomes will be followed by including both a radiolabelled phospholipid in the bilayer and a radiolabelled soluble marker in the aqueous space. The effect of size, surface charge, and lipid composition on the localization in both buffered saline and plasma will also be examined. For the in vivo system, both rats and mice will be used to determine the distribution of intra venous, intraperitoneal, and intrarterial injected magnetosomes. The effect of a directed external magnetic field on the localization of magnetosomes into different regions of the body will be established. Strategies to increase localized blood flow such as heating or vasodilators as a means of increasing the through put of magnetosomes will be investigated. Finally, I will examine the delivery and antitumor effect of magnetosome encapsulated drugs against the Lewis lung carcinoma and the B-16 melanoma tumor systems. In these models, the mode of injection of the malignant cells can lead to a localized tumor that after a characteristic time period can metastasize. Thus, they are excellent models to investigate the efficiency of magnetosomes as a targeted drug delivery system.